The overall goal of this project is to develop and experimentally test a neural model of the brain interactions underlying the production of speech sound sequences. In particular, we will focus on several brain regions thought to be involved in motor sequence production, including the lateral prefrontal cortex, ventral premotor cortex, supplementary motor area (SMA), pre-SMA, basal ganglia, cerebellum, and thalamus. Each of these brain regions will be mathematically modeled with equations governing neuron activities, and the interactions between the regions will be modeled with equations governing synaptic strengths. The resulting model will be implemented in computer software and combined with an existing neural model of speech sound production to allow generation of simulated articulator movements for producing speech sound sequences. The results of these computer simulations will be compared to existing kinematic and functional neuroimaging data. We also propose four functional magnetic resonance imaging (fMRI) experiments and two associated behavioral experiments specifically designed to test key hypotheses of the model, to test between the model and competing hypotheses, and to fill in gaps in the existing neuroimaging literature. The project involves two highly integrated subprojects. (1) Creating and testing a neural model of speech sequence production. The primary aim of this subproject is to develop a model of the neural circuits involved in the properly ordered and properly timed production of speech sound sequences, such as a sequence of syllables making up a sentence. The model incorporates a wide range of experimental data into a unified account of the interactions between SMA, pre-SMA, ventral premotor cortex, lateral prefrontal cortex, basal ganglia, and thalamus in sound sequence generation. Hypotheses concerning the generation of syllable "frames" and the storage of sound sequences in working memory are tested in two fMRI experiments that will be used to guide model development. (2) Investigating the learning of new speech sequences. The primary aim of this subproject is to further develop the model created in Subproject 1 to incorporate the effects of practice on the neural circuits underlying speech sound sequence generation. This investigation focuses on the contribution of cerebellar and basal ganglia circuits to the learning of novel syllables and sequences of syllables, and associated behavioral and fMRI experiments test key hypotheses concerning the changes in neural processing underlying sound sequence learning. We believe this integrated approach of computational neural modeling and functional brain imaging will provide a much clearer mechanistic account of the neural processes underlying speech production in normal speakers and individuals with communication disorders that involve problems in the initiation and/or sequencing of speech, such as apraxia of speech and stuttering. [unreadable] [unreadable] [unreadable]